Interpretive Summary: Feeding low (deficient) amounts of the trace element nickel to laboratory animals has been shown to impact vitamin B12 metabolism. Because the metabolism of vitamin B12 and folic acid are so interrelated, an experiment was performed to determine the effects of low dietary nickel on folic acid metabolism. Formiminoglutamic acid (FIGLU), a metabolite of the amino acid histidine, is commonly used as an indicator of folic acid status; during folic acid deficiency, urinary FIGLU excretion is markedly increased. S-adenosylmethionine (SAM), a metabolite of the amino acid methionine, is a compound that plays a crucial role in numerous metabolic pathways. The liver concentration of SAM is decreased in folic acid deficiency. Results from this experiment showed that feeding low dietary nickel caused a further increase in the urinary excretion of FIGLU and a further decrease in the liver concentration of SAM typically associated with folic acid deficiency. This would indicate that nickel is affecting some process in folic acid metabolism that is common to both FIGLU and SAM. This research indicates that nickel has a physiological role, possibly related to folic acid metabolism. Future research will help determine the site of action of nickel in folic acid metabolism and eventually the importance of nickel in human nutrition.

Technical Abstract:
A previous experiment using rats indicated that dietary nickel, folic acid, and their interaction affected variables associated with one-carbon metabolism. That study used diets that produced only mild folate deficiency. Thus, an experiment was performed to determine the effect of a severe folate deficiency on nickel deprivation in rats. A 2 x 2 factorially arranged experiment used groups of six weanling Sprague-Dawley rats. Dietary variables were nickel, as NiCl2 6H2O, 0 or 1 ug/g; and folic acid, 0 or 4 mg/kg. All diets contained 10 g succinylsulfathiazole/kg to suppress microbial folate synthesis. The basal diet contained less than 20 ng nickel/g. After 58 d, an interaction between nickel and folate affected the urinary excretion of formiminoglutamic acid (FIGLU) and the liver concentration of S-adenosylmethionine (SAM). Because of this finding, it is proposed that the physiological function of nickel is related to the common metabolism shared by SAM and FIGLU. Possibly the physiological function of nickel could be related to the tissue concentration of 5-methyltetrahydrofolate (MTHF) or tetrahydrofolate (THF).